{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:48:22Z","timestamp":1790725702406,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["306008\/2022-0"],"award-info":[{"award-number":["306008\/2022-0"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["303164\/2022-0"],"award-info":[{"award-number":["303164\/2022-0"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["405394\/2023-3"],"award-info":[{"award-number":["405394\/2023-3"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["303940\/2022-0"],"award-info":[{"award-number":["303940\/2022-0"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["441128\/2023-8"],"award-info":[{"award-number":["441128\/2023-8"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["404780\/2021-0"],"award-info":[{"award-number":["404780\/2021-0"]}]},{"name":"Conselho Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014Brasil-CNPq","award":["303438\/2021-5"],"award-info":[{"award-number":["303438\/2021-5"]}]},{"name":"Funda\u00e7\u00e3o Cearense de Apoio ao Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico\u2014FUNCAP UNIVERSA","award":["UNI-0210-00337.01.00\/23"],"award-info":[{"award-number":["UNI-0210-00337.01.00\/23"]}]},{"name":"FUNCAP-INTERNACIONALIZA\u00c7\u00c3O","award":["ITR-0214-00060.01.00\/23"],"award-info":[{"award-number":["ITR-0214-00060.01.00\/23"]}]},{"name":"PDCTR","award":["DCT-0182-00048.02.00\/21"],"award-info":[{"award-number":["DCT-0182-00048.02.00\/21"]}]},{"name":"PDCTR","award":["04879791\/2022"],"award-info":[{"award-number":["04879791\/2022"]}]},{"DOI":"10.13039\/501100005283","name":"FUNCAP","doi-asserted-by":"crossref","award":["BP5-0197-00174.01.00\/22"],"award-info":[{"award-number":["BP5-0197-00174.01.00\/22"]}],"id":[{"id":"10.13039\/501100005283","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005283","name":"FUNCAP","doi-asserted-by":"crossref","award":["FPD-0213-00369.01.00\/23"],"award-info":[{"award-number":["FPD-0213-00369.01.00\/23"]}],"id":[{"id":"10.13039\/501100005283","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: The increasing prevalence of multidrug-resistant Staphylococcus aureus represents a major clinical challenge, primarily driven by the acquisition of multiple resistance mechanisms. Among these, efflux pumps such as NorA play a pivotal role in quinolone resistance by promoting active drug extrusion and reducing intracellular antibiotic levels. This study evaluated the synthetic chalcone CMA4DMA as a potential NorA efflux pump inhibitor and modulator of bacterial resistance. Methods: Antimicrobial susceptibility assays were conducted against S. aureus SA1199 (wild-type) and SA1199B (NorA-overexpressing) strains. The minimum inhibitory concentration (MIC) of CMA4DMA and its modulatory effects on norfloxacin and ethidium bromide were determined. Efflux inhibition was assessed by ethidium bromide accumulation and SYTOX Green assays. Molecular docking and in silico ADMET analyses were performed to predict binding affinity and pharmacokinetic parameters. Results: CMA4DMA exhibited no intrinsic antibacterial activity (MIC \u2265 1024 \u00b5g\/mL) but reduced the MIC of norfloxacin from 32 to 8 \u00b5g\/mL and that of ethidium bromide from 32 to 8 \u00b5g\/mL in SA1199. In SA1199B, reductions from 64 to 16 \u00b5g\/mL and from 64 to 32 \u00b5g\/mL were observed, respectively. Fluorescence increased by 15% without affecting membrane integrity. Docking revealed a binding affinity of \u22127.504 kcal\/mol, stronger than norfloxacin (\u22127.242 kcal\/mol), involving key residues Leu218, Ile309, Arg310, and Ile313. ADMET data indicated high intestinal absorption (88.76%) and permeability (Papp = 1.38 \u00d7 10\u22125 cm\/s). Conclusions: CMA4DMA effectively restored norfloxacin susceptibility in resistant S. aureus strains, highlighting its potential as a promising scaffold for developing novel efflux pump inhibitors and antibiotic adjuvants.<\/jats:p>","DOI":"10.3390\/ph18111629","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:02:01Z","timestamp":1761670921000},"page":"1629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of the Activity of Amino Chalcone Against Staphylococcus Strains Harboring Efflux Pumps"],"prefix":"10.3390","volume":"18","author":[{"given":"Isyd\u00f3rio Alves","family":"Donato","sequence":"first","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Rodrigues dos Santos","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8209-0705","authenticated-orcid":false,"given":"Antonio Henrique","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suieny Rodrigues","family":"Bezerra","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ray Silva","family":"Almeida","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Chemical Biology, Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1316-7064","authenticated-orcid":false,"given":"C\u00edcera Datiane de Morais","family":"Oliveira-Tintino","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Chemical Biology, Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-0141","authenticated-orcid":false,"given":"Isaac Moura","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Chemical Biology, Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewerton Yago de Sousa","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Yasmin C\u00e2ndido de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Ferdinando","family":"Cajazeiras","sequence":"additional","affiliation":[{"name":"Chemistry Program, Vale do Acara\u00fa State University (UVA), Sobral 62040-370, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayza Maria Lima","family":"Dias","sequence":"additional","affiliation":[{"name":"Chemistry Program, Vale do Acara\u00fa State University (UVA), Sobral 62040-370, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3376-0789","authenticated-orcid":false,"given":"Jesyka Macedo","family":"Guedes","sequence":"additional","affiliation":[{"name":"Chemistry Program, Vale do Acara\u00fa State University (UVA), Sobral 62040-370, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica H\u00edade Silva","family":"Cristino","sequence":"additional","affiliation":[{"name":"Chemistry Program, Vale do Acara\u00fa State University (UVA), Sobral 62040-370, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-8775","authenticated-orcid":false,"given":"Emmanuel Silva","family":"Marinho","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences, State University of Cear\u00e1 (UECE), Fortaleza 60714-903, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rcia Machado","family":"Marinho","sequence":"additional","affiliation":[{"name":"Graduate Program in Natural Sciences, State University of Cear\u00e1 (UECE), Fortaleza 60714-903, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5527-164X","authenticated-orcid":false,"given":"H\u00e9lcio Silva dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Chemistry Program, Vale do Acara\u00fa State University (UVA), Sobral 62040-370, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-4207","authenticated-orcid":false,"given":"Henrique Douglas Melo","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology and Molecular Biology, Department of Chemical Biology, Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7733-9331","authenticated-orcid":false,"given":"Saulo Relison","family":"Tintino","sequence":"additional","affiliation":[{"name":"Laboratory of Semiarid Bioprospecting (LABSEMA), Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1065-9581","authenticated-orcid":false,"given":"Irwin Rose Alencar","family":"de Menezes","sequence":"additional","affiliation":[{"name":"Brazil National Institute of Science and Technology of the Health Economic\u2013Industrial Complex (iCEIS), Laboratory of Phamacology and Chemical Molecular, Department of Chemical Biology, Regional University of Cariri (URCA), Crato 63105-000, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Assis Bezerra","family":"da 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